The purpose of the proposed Phase I study is to explore a novel approach for influenza virus vaccination by using microencapsulated antigen administered by the oral or intranasal route in order to induce a protective mucosal immune response. Mice will be immunized with purified influenza virus type A H3N2 (Udorn) free in solution or encapsulated in biodegradable microspheres, by oral, intranasal, or systematic routes. The levels and isotype of the induced, antigen-specific immunoglobulins will be determined in sera and secretion collected from the immunized mice. The data obtained will be correlated with the form by which the antigen was delivered (free in the solution or in microspheres) and with the route of administration (systemic, oral, or intranasal). These studies are expected to provide information concerning the most effective route for induction of antibodies with a protective role against influenza virus infections. Potential advantages for using biocompatible and biodegradable microspheres as an antigen delivery vehicle include: protection and controlled release of relatively high amounts of antigen, an adjuvant effect, and selective stimulation of secretory or systemic immune response according to the size of microspheres. After establishing the immunogenicity of microencapsulated influenza virus in mice in Phase I research, the studies will be continued in Phase II in another animal model, squirrel monkeys. This model is more suitable for assessment of vaccine efficacy because of the similarities between monkey and human immune systems and because of the availability of a strain of influenza virus (Udorn) adapted to be infective in monkeys.